Fluorescent chemosensors for metals based on dipyrrins

Abstract

The present invention is a new class of fluorescent sensor with unprecedented sensitivity, selectivity and synthetic efficiency for the identification and qualitative and quantitative detection of transition metal ions. The chemosensing properties are based on an internal charge transfer mechanism or photo-induced electron transfer and are effective in vitro. The chemosensor comprises one or more electron donating dipyrrin functionalities linked to an electron withdrawing functionality. The chemosensor forms a stable transition metal complex through internal charge transfer between the electron donating functionality and the target transition metal, which results in measurable fluorescence. Specific examples for sensing zinc and copper ions are described.

1. A composition suitable for quantitative and qualitative sensing of +2 transition metals using ratiometric fluorescence capable of forming a stable transition metal complex through internal charge transfer with a target transition metal, and fluorescing in a measurable manner in the presence of the target transition metal, comprising:
 a. a metal binding, electron donating dipyrrin functionality; 
 b. an electron withdrawing functionality, wherein the electron donating functionality is linked to the electron withdrawing functionality; and 
 c. an attachment base to which the chemosensor can be fixedly attached, the composition comprising the formula: 
 
       
         
           
           
               
               
           
         
       
       wherein R 3  and R 5  comprise phenyl groups, R 4  comprises a 2-(8-hydroxyquinoline)group, and R 1  and R 2 , and R 6  and R 7  comprise fused 1,2(7-methoxytetrahydronaphthalene). 
     
     
       2. The composition according to  claim 1  wherein R 2  and R 3 , and R 5  and R 6 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di-4,6-nitrophenyl), 1,2-(tri-4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di-4,6-hydroxyphenyl), 1,2-(tri-4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl; and
 R 1 , R 4  and R 7 , independently from each other, are selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
 
     
     
       3. The composition according to  claim 1  wherein R 1  and R 2 , and R 6  and R 7 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di-4,6-nitrophenyl), 1,2-(tri-4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di-4,6-hydroxyphenyl), 1,2-(tri-4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl 1-pyreneyl, 2-pyreneyl, Leucine connected through N and C termini, 1,4-pyranosyl, 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclopentyl, 1,2-cyclohexyl, 1,2-cycloheptyl, 1,2-cyclooctyl, 1,2-cyclononyl, 1,2-cyclodecyl, 1,2-[4.4.0]cyclodecane, 1,2-[2.2.1]cycloheptane, 1,2(4-pyridinyl), 1,2-(4-quinolinyl), 1,2-(9-acridinyl) and R 3 , R 4  and R 5 , independently from each other, are selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1[-4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       4. The composition according to  claim 1  wherein R 2  and R 3 , and R 6  and R 7 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di-4,6-nitrophenyl), 1,2-(tri-4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di-4,6-hydroxyphenyl), 1,2-(tri-4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl, cyclohexyl and R 1  , R 4  and R 5 , independently from each other, are selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C, alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       5. The composition according to  claim 1  wherein R 1  and R 2 , and R 5 and R 6 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di-4,6-nitrophenyl), 1,2-(tri-4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di-4,6-hydroxyphenyl), 1,2-(tri-4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl; and R 3 , R 4  and R 7 , independently from each other, are selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       6. The composition according to  claim 1  wherein R 1 , R 2 , R 3 , R 5 , R 6  and R 7 , are hydrogen, and R 4  is selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       7. The composition according to  claim 1  wherein R 2  and R 3 , and R 5  and R 6 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di4,6-nitrophenyl), 1,2-(tri-4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di4,6-hydroxyphenyl), 1,2-(tri4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl; R 1  and R 2  are hydrogen and R 4  is selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       8. The composition according to  claim 1  wherein R 1  and R 2 , and R 6  and R 7 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di4,6-nitrophenyl), 1,2-(tri4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di4,6-hydroxyphenyl), 1,2-(tri4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl; R 3  and R 6  are hydrogen and R 4  is selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       9. The composition according to  claim 1  wherein R 2  and R 3 , and R 6  and R 7 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di4,6-nitrophenyl), 1,2-(tri4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di4,6-hydroxyphenyl), 1,2-(tri4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl; R 1  and R 5  are hydrogen and R 4  is selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       10. The composition according to  claim 1  wherein R 1  and R 2 , and R 5  and R 6 , independently from each other, are selected from the group of fused structures consisting of phenyl, 1,2-(4-nitrophenyl), 1,2-(di4,6-nitrophenyl), 1,2-(tri4,5,6-nitrophenyl) 1,2-(phen-4-ol), 1,2-(di4,6-hydroxyphenyl), 1,2-(tri4,5,6-hydroxyphenyl), 1,2-napthyl, 1,2-(nitro-3-napthylene), 1,2-anthraceneyl, 1,2-pyreneyl, 1,2-cyclohexyl, 1,2-pyridinyl, 1,2-quinolinyl, 1,2-acridinyl; R 3  and R 7  are hydrogen and R 4  is selected from the group consisting of hydrogen, alcohol, methoxy, C 1 -C, alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, Leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclononyl, 1-cyclodecyl, 1-[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       11. The composition according to  claim 1  wherein R 2 , R 3 , R 5  and R 6  are hydrogen; and R 1 , R 4  and R 7 , independently from each other, are selected from the group consisting of hydroxyl, methoxy, tert-butyl, isobutyl and isopropyl, hydrogen, alcohol, methoxy, C 1 -C 7  alkyl, nitro, phenyl, nitro-4-phenyl, di-2,4-nitrophenyl, tri-2,4,6-nitrophenyl phen-4-ol, di-2,4-hydroxy, tri-2,4,6-hydroxyphenyl, 1-napthyl, 2-napthyl, nitronapthylene, 1-anthraceneyl, 2-anthraceneyl, 3-anthraceneyl, 1-pyreneyl, 2-pyreneyl, leucine attached at the nitrogen, peptide, 1-pyranosyl, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptyl, 1-cyclooctyl, 1-cyclonoriyl, 1-cyclodecyl,  1 -[4.4.0]cyclodecane, 1-[2.2.1]cycloheptane, 4-pyridinyl, 4-quinolinyl, 9-acridinyl, 1-(4-phenyl(1,3-dibutenyl)), 1-(6-phenyl (1,3,5-trihexenyl), 1-(8-phenyl (1,3,5,7-tetraoctenyl) and 1-(10-phenyl 1,3,5,7,9-pentadecenyl), 1-glucosyl. 
     
     
       12. The composition according to  claim 1  wherein the attachment base comprises materials selected from a group consisting of glass, plastic, quantum dots and polymer. 
     
     
       13. The composition according to  claim 5  wherein the attachment base comprises materials selected from a group consisting of glass, plastic, quantum dots and polymer.